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An antibody-supermolecule conjugate for tumor-specific targeting of tumoricidal methylated β-cyclodextrin-threaded polyrotaxanes

Journal of Materials Chemistry B, ISSN: 2050-7518, Vol: 8, Issue: 31, Page: 6975-6987
2020
  • 17
    Citations
  • 0
    Usage
  • 10
    Captures
  • 1
    Mentions
  • 14
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    17
  • Captures
    10
  • Mentions
    1
    • News Mentions
      1
      • 1
  • Social Media
    14
    • Shares, Likes & Comments
      14
      • Facebook
        14

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Article Description

We previously found that acid-labile polyrotaxane containing methylated β-cyclodextrin (Me-PRX) induces endoplasmic reticulum (ER) stress-related autophagy and autophagic cell death. Me-PRX-induced autophagic cell death occurs even in apoptosis-resistant cells; tumor-targeted Me-PRX delivery could thus be an effective cancer treatment approach. In this study, antibody-supermolecule conjugates, consisting of a tumor-specific antibody and Me-PRX, were designed to achieve a tumor-specific delivery of Me-PRX. Trastuzumab, a monoclonal antibody against HER2 expressed in various malignant tumors, was selected as a tumor-targeting antibody, and phenyl maleimide group-modified Me-PRX (Mal-Me-PRX) was conjugated to the cysteine residue of the reduced Trastuzumab to obtain a Trastuzumab-Me-PRX conjugate (Tras-Me-PRX). The cellular association of Tras-Me-PRX to HER2-expressing tumor cells was remarkably greater than that of unmodified Me-PRX. Moreover, Tras-Me-PRX effectively reduced the viability of HER2-expressing tumor cells at a lower concentration compared to the unmodified Me-PRX. In conclusion, antibody-Me-PRX conjugates are regarded as a new class of antibody-drug conjugates that would contribute to the chemotherapy of cancers. This journal is

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